The pathogenesis of chronic rhinosinusitis (CRS) is characterized by mucosal inflammation with activated epithelial cells and T cells. Exciting new studies from our laboratories show that nasal epithelial cells express B7 homologs, specialized molecules that mediate T cell activation. Our recent in vitro studies show that selected B7 homologs are increased by cytokines and decreased by glucocorticoids. We hypothesize that epithelial cell surface molecules (B7 homologs, HLA-DR, Fas, Fas ligand and CD40) can serve as markers of disease and that exacerbation of sinonasal disease will be associated with increased epithelial costimulators. Based upon our in vitro findings, we hypothesize and that glucocorticoid treatment will inhibit the epithelial response. The primary goal of the studies described in this proposal is to test these hypotheses using a host of specific and reproducible assays to quantitate costimulator expression. Studies in Aim 1 will quantitate expression of costimulatory molecules on sinonasal epithelial cells from control and 4 subgroups of CRS patients with defined disease (CRS alone, CRS with allergic rhinitis, CRS with asthma and CRS with both asthma and aspirin sensitivity (Samter's triad)). Expression of costimulators will be analyzed by Taqman PCR and flow cytometry. These studies will be reinforced by studies employing immunohistochemistry of surgical tissue from the same subjects. Studies in Aim 2 will determine levels of epithelial costimulatory molecule expression in patients before, during and after exacerbations to test the hypothesis that disease exacerbation will be associated with alterations of costimulator expression. We will also examine the in vivo effect of intranasal glucocorticoid treatment on costimulator expression. Studies in Aim 3 will utilize cultured epithelial cells to determine the influence of stimuli likely to participate in CRS (cytokines, toll-like receptor ligands, human rhinovirus and fungal antigens) on costimulator expression and to probe the mechanism of the effect. It is our hope that these studies will give new insight into the factors that modulate epithelial cells in chronic rhinosinusitis.